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Biomedical subjects

M Wehling

Publications and source records attributed to M Wehling.

At least 19 recordsLinked to original sources
PubMed2005

Aldosterone blunts human baroreflex sensitivity by a nongenomic mechanism.

BACKGROUND: Impaired baroreflex sensitivity (BRS) is a negative predictive factor of mortality in cardiovascular disease. Aldosterone has been shown to decrease BRS in humans and animal models. However, the mode of aldosterone action, whether genomic or nongenomic has not been determined. Therefore, we conducted a clinical study to examine whether BRS, as measured by the phenylephrine method, is impaired in humans by aldosterone by a nongenomic mechanism. METHODS: In a randomised, double-blinded, fourfold cross-over trial in 16 healthy male volunteers, BRS was tested 15 minutes after initiation of a continuous infusion of aldosterone (3 microg/minute) or placebo. 6 hours earlier, this period was preceded by an injection of either canrenoate (400 mg) or placebo. RESULTS: BRS was 34.6 +/- 4.7 ms/mm Hg in the placebo/placebo period. It was significantly blunted in the placebo/aldosterone (25.5 +/- 1.8 ms/mm Hg) as well as in the canrenoate/placebo (24.0 +/- 1.5 ms/mm Hg) and the canrenoate/aldosterone (25.4 +/- 2.5 ms/mm Hg) periods. CONCLUSION: These data suggest that the decreased BRS caused by aldosterone is due to a rapid, thus presumably nongenomic mechanism, as these effects occur in a time frame that excludes genomic aldosterone effects at large. The mineralocorticoid receptor (MR) antagonist canrenoate does not block these effects, but blunts BRS by itself.

Adult↗
PubMed2005

Classic and non-classic progesterone receptors are both expressed in human spermatozoa.

Progesterone is one of the physiological inducers of the acrosome reaction in mammalian spermatozoa. The receptor that responds to progesterone is not yet identified, and its properties differ in many aspects from the properties of the classic nuclear progesterone receptor, suggesting the participation of a novel or non-classic receptor. In this study, we investigated the expression of a novel progesterone-binding protein (hmPR1/PGMRC1) and its ortholog (hmPR2/PGMRC2), which have previously been identified in liver microsomes and are considered receptor candidates, along with the nuclear progesterone receptor. The purification procedure was optimized with special emphasis on the control of leukocyte contamination in single donor samples. The results indicate that all three proteins are expressed in human sperm, as transcripts have been detected in 46 %, 42 % and 37.5 % of individual samples, respectively (n = 24).

Cell Separation↗
PubMed2005

Impact of ABO blood groups on tirofiban mediated inhibition of platelet function.

Previous investigations revealed that ABO blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group O as compared to subjects with blood group A, B or AB which might result in a reduced inhibition of platelet aggregation. The aim of the present in-vitro-investigation was to elucidate the impact of ABO blood group dependent vWF concentrations on tirofiban mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100 at baseline and at increasing concentrations of tirofiban and stratified for blood group O vs. A. If measured with the collagen/epinephrine cartridge, blood group O was associated with a prolonged mean baseline closure time in comparison with blood group A (175.8 +/- 64.9 s vs. 121.4 +/- 33.4 s, p = 0.037) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no differences in closure time (227.6 +/- 76.1 s vs. 223.9 +/- 81.9 s, p = 0.96) could be found in the presence of tirofiban (0.1 microg/ml). Thus, tirofiban mediated GP IIb/IIIa receptor antagonism as determined with the PFA-100 seems to be independent on plasma concentration of vWF.

ABO Blood-Group System↗
PubMed2004

[Recommendations for statin therapy in the elderly].

Elderly patients are significantly less likely to receive statins than younger patients possibly because of doubts regarding compliance or concerns regarding the increased likelihood of adverse events and drug interactions. Poor compliance can be expected especially in patients suffering from dementia or depression as well as those whose stage of cardiovascular disease exhibits few symptoms. On the other hand, the clinical significance of CHD events is high in the elderly, and 80% of coronary deaths occur in patients aged over 65 years. The average statistical life expectancy of elderly and old patients is often underestimated. The HPS and PROSPER studies showed that statins reduce mortality and morbidity even in very elderly individuals with a high global cardiovascular risk and/or CAD. Patients up to the age of 79 years should be treated according to the same guidelines as younger patients. Statin therapy should only be considered for patients aged 80 years and older who are at a very high risk for cardiovascular events.

Aged↗
PubMed2004

[Celecoxib in the symptomatic treatment of active osteo- or rheumatoid arthritis. Results of a post-marketing surveillance].

BACKGROUND AND OBJECTIVE: The introduction of cyclooxygenase (COX)-2 selective drugs now offers physicians the possibility of a adequate analgesic and anti-inflammatory therapy. Drug induced side effects typically associated with NSAIDs are reduced. Using a post-marketing surveillance study (PSS) efficacy and tolerability of the COX-2-selective drug Celecoxib was evaluated. Patients were not restricted in the use of other medication. PATIENTS AND METHODS: By means of a prospective, non-intervening PSS patients mainly suffering from musculoskeletal conditions such as osteoarthritis (70.5 %) or rheumatoid arthritis (19.6 %) were examined by about 12,000 physicians. The median observation period was almost 5 weeks. RESULTS: In total 70236 patients (42 % males, 58 % females, mean age 60.3 years) were assessed. About 87 % of the patients were adequately treated with a daily dose of 200 mg. The tolerability of the treatment was judged to be "good" to "very good" by the physicians in 97 % and by the patients in 96 % of the cases. The overall incidence of undesirable events (UE) with or without potential causal relationship with the study medication was 2.8 % (1,955 patients), severe UEs manifesting in 0.3 % (223) of all patients. CONCLUSIONS: Overall, the PSS confirms the evident subjective efficacy and tolerability by both the physician's and the patient's overall assessment.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Diabetes and cardiovascular risk evaluation and management in primary care: progress and unresolved issues - rationale for a nationwide primary care project in Germany.

This review highlights established and more recently recognized risk factors for coronary heart disease (CHD) relevant for patients seen in primary care, emphasizing the key role of diabetes mellitus type 2. Recent trends in risk factor research as well as current methods of risk stratification, and new systemic markers are discussed. Beyond the need for more forceful public health strategies to improve early recognition and intervention, the necessity of an integrated comprehensive investigation of the overall characteristics of cardiovascular disease, especially in primary care patients as a prerequisite for future concerted actions is pointed out. Based on this, a large-scale epidemiological investigation focusing on CHD and diabetes in the primary care sector is suggested.

Cardiovascular Diseases↗
PubMed2004

Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitis.

BACKGROUND: Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge. METHODS: Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry. RESULTS: Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P<0.05) and by 18% following methylprednisolone (P=0.07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P<0.05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P<0.05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P<0.05 for both time points following betamethasone). CONCLUSION: This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect.

Allergens↗
PubMed2003

[Drug therapy of elderly patients from the viewpoint of the clinical pharmacologist].

Polypragmasy (polypharmacotherapy) is often due to the frequent incidence of multimorbidity among elderly patients. This may evoke unpredictable drug-interactions, which often become a reason for hospitalization. Additional medications might be the consequence. Geriatric patients are often characterized by variant pharmacokinetic parameters. Individualized drug-therapy should take into consideration not only the patients' age, liver and kidney functions but also the individual variability of hepatic metabolization and drug-resorption in the intestine based on genetic polymorphisms. Summing up, it is very important to verify a consisting or a new drug-therapy concerning its risk-benefit ratio and if it is needed, to omit or change some of the medications.

Aged↗
PubMed2003

[Pharmacogenomics. What is relevant for the internal medicine specialist?].

Epidemiological observational studies have shown existing interindividual and interethnical differences in drug metabolism. This results in a great variety of effects and side effects of drugs. One reason for these variabilities are genetic polymorphisms which occur on the basis of single-nucleotide exchanges or insertional and deletional mutations. Such mutations may involve transport proteins or metabolizing enzymes of phase I and phase II reactions, as cytochrome P450, glucuronidases and enzymes which metabolize cytostatics. The differences in pharmacokinetics and pharmacodynamics have an impact on therapeutical outcome. Dosage adjustments should be undertaken before the initiation of therapy in reflection of modern genotyping. This is particularly important in oncology to avoid life-threatening adverse drug reactions. Examples of cardiovascular and neurological diseases are presented to demonstrate the impact of genetic polymorphisms on the incidence and prevalence of diseases as well as the responses to medications like beta blockers, ACE inhibitors and psychotropic drugs. Finally, additional factors are summarized, which may contribute to the large diversity of drug reactions.

Cytochrome P-450 Enzyme System↗
PubMed2003

Nongenomic effects of aldosterone on human renal cells.

The development of chronic renal insufficiency may be partially mediated by the nongenomic action of aldosterone. Here we investigate whether aldosterone could evoke a nongenomic action in primary cultures of human renal cells. Intracellular Ca(2+) ([Ca(2+)](i)) and cAMP were measured in human mesangial cells (MC), glomerular visceral epithelial cells (GVEC), and proximal and distal tubular epithelial cells (Ptec and Dtec) in the presence of aldosterone (10-100 nmol/liter) by fura-2 fluorescence and RIA, respectively. In MC, Ptec, and Dtec, aldosterone increased [Ca(2+)](i) within 1 min, whereas in GVEC, only a minor effect was found. Preincubation of cells with spironolactone did not blunt this effect. Hydrocortisone, used at a concentration 100-fold higher than that of aldosterone, did not affect [Ca(2+)](i.) In MC, Ptec, and Dtec, a dose-dependent increase ( approximately 1.3- to 1.5-fold) in intracellular cAMP levels was found. These data demonstrate a nongenomic action of aldosterone in human MC, Ptec, and Dtec. As these effects occur at concentrations close to free plasma aldosterone levels in man, they may be of physiological relevance and may contribute to renal injury.

Aldosterone↗
PubMed2002

[Questionable group concept. How interchangeable are so-called analog drug preparations?].

Medical drugs are usually grouped together because they exhibit identical or similar chemical and pharmacological properties. Thus, for example, all known statins lower morbidity and mortality in coronary patients. In the meantime, three beta blockers have been shown to have a life-prolonging effect in mild-to-moderate cardiac insufficiency. The question is: to what extent are the preparations interchangeable? The beta blockers in particular manifest numerous other properties--such as beta 1 selectivity, vasodilatory or antioxidative actions which, under certain circumstances may even be decisive for the success or failure of treatment. The mortality-lowering effect of high-dose ACE inhibitors in patients with a high cardiovascular risk has to date, been shown only for a single preparation. For others, the high dose (effect) has yet to be confirmed. Also, with every new substance, a new side effect profile is introduced, which may result from the tiniest alteration to the active agent molecule, but also by a different preparation method. In consequence, unexpected effects, such as allergic reactions, may occur. This not only makes the grouping of similar substances, but also the interchange of "me-too" or generic preparations, problematic.

Adrenergic beta-Antagonists↗
PubMed2002

Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns.

BACKGROUND: Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease (CHD) is far from optimal. The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels. METHODS: Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication. Data are derived from a multicenter, randomized, open-label, parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany. Medical history, physical examination, and serum lipid levels were obtained at the beginning of the washout phase (Week -6) and at the end of the washout phase (Week -1, i.e., 5 weeks after the discontinuation of all prior lipid-lowering medications). The data at Week -6 represented the lipid levels under real life conditions. The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at Week -6 was 173.4 +/- 42.5 mg/dl. Only 176 (6.2%) of 2,856 CHD patients were found to meet the target LDL-C level of <115 mg/dl at Week -6, only 76 (2.7%) patients had LDL-C levels <100 mg/dl, and 363 (12.7%) patients had LDL-C levels <130 mg/dl. After discontinuation of all prior lipid-lowering medications, mean LDL-C increased to 187.2 +/- 44.0 mg. This means that only a marginal 7.4% reduction in LDL-C level was achieved under real life treatment conditions. This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment (65.5% of patients did not receive any medication at all) and inadequate dosing. With respect to the effect on LDL-C and total cholesterol, statins alone were superior to fibrates. CONCLUSION: The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany. Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians. Available treatment guidelines should be better implemented.

Adult↗